Volume 15 Issue 5, May 2014

The receptor CD96 inhibits cytokine production by natural killer cells in mice and antagonizes activation mediated by the receptor CD226.

CTLA-4 is a potent inhibitor of T cell population expansion. The PIX-GIT2-PAK2 complex is recruited to the cytoplasmic domain of CTLA-4 via the kinase PKC-η, which suggests a previously unrecognized aspect of signal transduction via CTLA-4 in immunoregulation.

Although it is generally considered a proinflammatory cytokine, interleukin 6 (IL-6) has anti-inflammatory effects in macrophages by sensitizing them to IL-4 through upregulation of the IL-4 receptor.

Cytokines and other environmental cues influence polarization of CD4⁺ helper T cells, but the signaling pathways that are involved are less clear. Recent findings show that signaling via an mTORC2-SGK1 kinase axis regulates T_H1–T_H2 cell-fate polarization.

The role of IL-6 in obesity-associated inflammation remains controversial. Bruening and colleagues identify signaling by IL-6 as an important determinant for the alternative activation of macrophages during inflammation.

The function of the lymphocyte-expressed receptor CD96 is almost entirely unknown. Smyth and colleagues demonstrate that it serves a key role in restraining activation of NK cells in part by competing with the activating receptor CD226 (DNAM-1).

Histone deacetylases (HDACs) are crucial regulators of cell identity. Ellmeier and colleagues show that HDAC1 and HDAC2 maintain CD4⁺ T cell lineage integrity by repressing Runx-CBFβ complexes in T_H1 cells but not in T_H2 cells.

Adaptors of the TRAF family are tumor-necrosis factor receptor–associated factors. So and colleagues show that TRAF5 negative regulates the IL-6 receptor signaling pathway, which limits the induction of proinflammatory CD4⁺ T cells.

The kinase SGK1 is a downstream target of mTORC2 signaling. Powell and colleagues show that SGK1 regulates T_H2 polarization by increasing the stability of the transcription factor JunB and antagonizing IFN-γ expression.

Signaling events at the T_reg cell immune synapse remain unknown. Altman and colleagues show that a CTLA-4–PKC-η signaling axis is required for contact-dependent suppression by T_reg cells.

The precise mechanisms of the thymic development T_reg cells are still being determined. Farrar and colleagues demonstrate that signals from a triumvirate of members of the tumor-necrosis factor receptor superfamily are critical for T_reg cell development in the thymus.